Methylation of histone tails is believed to be important for the establishment and inheritance of gene expression programs during development. Jarid2/Jumonji is the founding member of a family of chromatin modifiers with histone demethylase activity. Although Jarid2 contains amino acid substitutions that are thought to abolish its catalytic activity, it is essential for the development of multiple organs in mice. Recent studies have shown that Jarid2 is a component of the polycomb repressive complex 2 and is required for embryonic stem (ES) cell differentiation. Here, we discuss current literature on the function of Jarid2 and hypothesize that defects resulting from Jarid2 deficiency arise from a failure to correctly prime genes in ES cells that are required for later stages in development.